Pregnancy in women with Hereditary Angioedema due to C1-inhibitor deficiency: Results from the ITACA cohort study on outcome of mothers and children with in utero exposure to plasma-derived C1-inhibitor.

Background: In women with Hereditary Angioedema (HAE) due to C1-inhibitor (C1INH) deficiency (C1INH-HAE), pregnancy counseling and treatment can be challenging. Despite the evidence of the immediate favorable outcome and safety of plasma-derived (pd)C1INH concentrate, there are no data regarding any difference among women who underwent or not pdC1INH during pregnancy or on children with in utero exposure to pdC1INH. The present interview study aimed at analyzing outcome of C1INH-HAE mothers and children according to pdC1INH-exposure during pregnancies. Methods: C1INH-HAE women who experienced at least 1 pregnancy were included from seven centers of the Italian Network for Hereditary and Acquired Angioedema (ITACA). The interview study retrospectively analyzed pregnancies who underwent (group 1) or not (group 2) pdC1INH. The overall goals of the study included immediate and long-term outcomes, in terms of outcomes in the time interval between pregnancy and survey. Results: A total of 168 pregnancies from 87 included women were analyzed. At term delivery (>37 gestation-week, GW) has been registered in 73.8% of cases, while spontaneous abortion (SA) occurred in 14.2% of cases with a mean GW 7 ± 2. The group 1 including pdC1INH-treated pregnancies comprised a third of the cohort (51/168, time interval 1.5 ± 10.4 yrs), while the group 2 represented 69.6% (117/168, time interval 32.8 ± 14 yrs). The same prevalence of SA occurred when comparing group 1 (11.7%) with group 2 (15.4%) with a similar GW at SA. The group 1 was older at the pregnancy time and younger at the interview than the group 2 (P < 0.01 for both); moreover, the group 1 showed a higher prevalence of cesarean delivery (P < 0.0001). The overall prevalence of obstetrical syndromes was similar between two groups: however, gestational diabetes was described only in pdC1INH-untreated pregnancies. In utero pdC1INH-exposed children (n = 45) did not show differences compared with unexposed ones (n = 99) in neonatal short-term outcomes. Conclusion: Through appropriate management and counseling, most of C1INH-HAE women undergo successful pregnancy and delivery. For pregnant C1INH-HAE women being treated with pdC1INH, our findings are reassuring and might lead to an improvement of both the knowledge about treatments and the experience of HAE itself.

An unusual neurological presentation in a patient with primary hypereosinophilic syndrome.

Hypereosinophilic syndromes are characterized by an increased number of blood eosinophils (usually more than 1.5 × 109) infiltrating tissues and causing organ damage through over-production of pro-inflammatory cytokines with heterogeneous clinical presentation. Here we present a case of a 47 years old male, with an unremarkable previous medical history, with a sudden onset of subungual hemorrhage and low back pain. Admitted for right arm weakness and vomiting, was raised the suspicion of acute cerebrovascular syndrome, but a brain CT scan with angiogram and perfusion sequences did not show any signs of early ischaemic lesions; conversely, lab tests revealed an increased peripheral eosinophil blood count. Clinical conditions rapidly worsened and a brain MRI showed multiple sub-acute ischaemic lesions compatible with vasculitis while EEG was in favor of widespread cortical distress. Diagnosis of the hypereosinophilic syndrome was made through peripheral blood smear and osteo-medullar biopsy, which showed a rich prevalence of eosinophils. The molecular biology testing showed FIP1L1-PDGRA gene mutation. Despite the prompt therapy beginning with intravenous corticosteroids and tyrosine-kinase inhibitors with normalization of cell blood count in a few days, the patient remained in minimal consciousness. When facing unusual symptoms onset (low back pain with weakness in one limb) and a highly impaired WBC not consistent with other courses (such as infections, vasculitis, allergies, and other diseases involving the immune system) clinicians should take into account the possibility of a hematological disorder and treat it as soon as possible to avoid a poor prognosis.

Nailfold Videocapillaroscopy Findings in Bradykinin-Mediated Angioedema.

BACKGROUND AND OBJECTIVE: Hereditary angioedema with C1-inhibitor deficiency (C1-INH-HAE) and acquired angioedema related to angiotensin-converting enzyme (ACE) inhibitors (ACEI-AAE) are types of bradykinin-mediated angioedema without wheals characterized by recurrent swelling episodes. Recent evidence suggests that a state of "vascular preconditioning" predisposes individuals to attacks, although no data are available on possible structural alterations of the vessels. Objective: This study aims to compare the features of nailfold capillaries to highlight possible structural anomalies between patients affected by C1-INH-HAE and controls and between patients with ACEI-AAE and hypertensive controls. METHODS: We used nailfold videocapillaroscopy (NVC) to assess the following: apical, internal, and external diameter; loop length; intercapillary distance; and capillary density, distribution, and morphology. Plasma levels of vascular endothelial growth factor (VEGF) A, VEGF-C, angiopoietin (Ang) 1, and Ang2 were also measured. RESULTS: Compared with healthy controls (n=28), C1-INH-HAE patients (n = 34) were characterized by significant structural alterations of the capillaries, such as greater intercapillary distance (216 vs 190 µm), increased apical, internal, and external diameter (28 vs 22 µm; 22 vs 20 µm; and 81 vs 65 µm, respectively), decreased density (4 vs 5 capillaries/mm2), more irregular capillary distribution, and more tortuous morphology. Apical diameter was enlarged in patients with ≥12 attacks per year. In ACEI-AAE patients, NVC showed no alterations with respect to hypertensive controls. NVC performed in 2 C1-INH-HAE patients during attacks showed no changes compared with the remission phase. CONCLUSIONS: We detected major structural capillary alterations in C1-INH-HAE patients, thus confirming the involvement of microcirculation in the pathogenesis of angioedema.

Quantitative analysis of movements in facial nerve palsy with surface electromyography and kinematic analysis.

Facial nerve paralysis (FNP) has a significant effect on a person's quality of life. In individuals with FNP undergoing facial rehabilitation, methods to analyze the loss of function are useful in diagnosis, treatment and follow up. To propose a protocol with kinematic analysis coupled with sEMG to evaluate the outcomes of FNP, quantifying the excursion degrees of the facial muscles and symmetry of voluntary movements. 10 patients (Group A) were followed by diagnosis until the end of the rehabilitation program. Kinematic analysis of 20 healthy adults (group B) was performed as a starting point to have a normality range and to test intra-subject and inter- intra rater reliability. An optoelectronic system and sEMG wireless electrodes were used. In Group A, a significant improvement in the movement of frontalis muscle (P = 0.0118) after 4-week treatment from the beginning (T0) 9.8 ± 4.5 mm to the end of rehabilitation (T1) 16.3 ± 5.8 mm and orbicularis oris (P = 0.0143) from T0 14.8 ± 5.5 mm to T1 20.3 ± 3.3 mm and, a reduction of % of maximum voluntary contractions (MVC) at T1 for frontalis and orbicularis compared to T0. This protocol provides meaningful data in a simple, reliable and objective way for the functional assessment of patients with PNF.

Nailfold Videocapillaroscopy Findings in Bradykinin-Mediated Angioedema

Background: Hereditary angioedema with C1-inhibitor deficiency (C1-INH-HAE) and acquired angioedema related to angiotensin-converting enzyme (ACE) inhibitors (ACEI-AAE) are types of bradykinin-mediated angioedema without wheals characterized by recurrent swelling episodes. Recent evidence suggests that a state of “vascular preconditioning” predisposes individuals to attacks, although no data are available on possible structural alterations of the vessels. Objective: This study aims to compare the features of nailfold capillaries to highlight possible structural anomalies between patients affected by C1-INH-HAE and controls and between patients with ACEI-AAE and hypertensive controls.Methods: We used nailfold videocapillaroscopy (NVC) to assess the following: apical, internal, and external diameter; loop length; intercapillary distance; and capillary density, distribution, and morphology. Plasma levels of vascular endothelial growth factor (VEGF) A, VEGF-C, angiopoietin (Ang) 1, and Ang2 were also measured. Results: Compared with healthy controls (n=28), C1-INH-HAE patients (n = 34) were characterized by significant structural alterations of the capillaries, such as greater intercapillary distance (216 vs 190 μm), increased apical, internal, and external diameter (28 vs 22 μm; 22 vs 20 μm; and 81 vs 65 μm, respectively), decreased density (4 vs 5 capillaries/mm2), more irregular capillary distribution, and more tortuous morphology. Apical diameter was enlarged in patients with ≥12 attacks per year. In ACEI-AAE patients, NVC showed no alterations with respect to hypertensive controls. NVC performed in 2 C1-INH-HAE patients during attacks showed no changes compared with the remission phase. Conclusions: We detected major structural capillary alterations in C1-INH-HAE patients, thus confirming the involvement of microcirculation in the pathogenesis of angioedema (AU)

Antecedentes: Tanto el angioedema hereditario con deficiencia de inhibidor del C1 (C1-INH-HAE) como el angioedema adquiridorelacionado con los inhibidores de la ECA (ACEI-AAE), son dos tipos de angioedema mediados por bradicinina que cursan con episodiosde inflamación recurrente sin acompañarse de habones. Existe evidencia de la existencia de un estado de "preacondicionamiento vascular"que predispone a estos pacientes a los ataques, pero no hay datos disponibles sobre las posibles alteraciones estructurales de los vasos.Objetivo: Este estudio tiene como objetivo el evaluar las características de los capilares de la base ungueal para identificar posiblesanomalías estructurales en los pacientes afectados por C1-INH-HAE en comparación con la población sana, y en los pacientes con ACEIAAE en comparación con controles con hipertensión arterial.Métodos: Mediante videocapilaroscopia de la base ungueal (NVC), se evaluaron: los diámetros apical, interno y externo, la longitud delasa, la distancia intercapilar, la densidad capilar, su distribución y su morfología. También se midieron los niveles plasmáticos del factorde crecimiento endotelial vascular (VEGF)-A, VEGF-C, angiopoyetina (Ang)1 y Ang2.Resultados: En los pacientes con C1-INH-HAE (n = 34) se observaron alteraciones estructurales de los capilares significativas, en comparacióncon los controles sanos (n = 28): mayor distancia intercapilar (216 frente a 190 µm), aumento del diámetro apical, interno y externo(28 frente a 22 µm; 22 frente a 20 µm; y 81 frente a 65 µm, respectivamente), disminución de la densidad (4 frente a 5 capilares/mm2),distribución capilar más irregular y una morfología más tortuosa. El diámetro apical fue mayor en aquellos pacientes con ≥12 ataques/año. En los pacientes con ACEI-AAE, las NVC no mostraron alteraciones al ser comparadas con las de los controles hipertensos. Las NVC realizadas en dos pacientes ...(AU)

Rehabilitation of patients post-COVID-19 infection: a literature review.

Rehabilitation is important for patients with coronavirus disease 2019 (COVID-19) infection. Given the lack of guidelines in English on the rehabilitation of these patients, we conducted a review of the most recent reports. We performed this literature review using the principal research databases and included randomized trials, recommendations, quasi-randomized or prospective controlled clinical trials, reports, guidelines, field updates, and letters to the editor. We identified 107 studies in the database search, among which 85 were excluded after screening the full text or abstract. In total, 22 studies were finally included. The complexity of the clinical setting and the speed of spread of the severe acute respiratory syndrome coronavirus 2, which leads to rapid occupation of beds in the intensive care unit, make it necessary to discharge patients with COVID-19 who have mild symptoms as soon as possible. For these reasons, it is necessary to formulate rehabilitation programs for these patients, to help them restore physical and respiratory function and to reduce anxiety and depression, particularly patients with comorbidities and those who live alone or in rural settings, to restore a good quality of life.

Angiotensin-Converting Enzyme Inhibitor-Associated Angioedema: From Bed to Bench.

BACKGROUND AND OBJECTIVE: Angiotensin-converting enzyme inhibitor-associated angioedema (ACEI-AAE) affects 0.1%-0.7% of patients treated with ACEIs. While previous research suggests that angioedema attacks result from increased vascular permeability, the pathogenesis is not completely understood. Objective: This study aimed to describe the clinical, genetic, and laboratory parameters of ACEI-AAE patients and to investigate the role of vascular endothelial growth factors A and C (VEGF-A and VEGF-C), angiopoietins 1 and 2 (Ang1/Ang2), and secretory phospholipase A2 (sPLA2) in the pathogenesis of ACEI-AAE. METHODS: The clinical and laboratory data of ACEI-AAE patients were collected from 2 angioedema reference centers. Healthy volunteers and ACEI-treated patients without angioedema were enrolled to compare laboratory parameters. Genetic analyses to detect mutations in the genes SERPING1, ANGPT1, PLG, and F12 were performed in a subset of patients. RESULTS: A total of 51 patients (57% male) were diagnosed with ACEI-AAE. The average time to onset of symptoms from the start of ACEI therapy was 3 years (range, 30 days-20 years). The most commonly affected sites were the lips (74.5%), tongue (51.9%), and face (41.2%). Switching from ACEIs to sartans was not associated with an increased risk of angioedema in patients with a history of ACEIAAE. VEGF-A, VEGF-C, and sPLA2 plasma levels were higher in ACEI-AAE patients than in the controls. Ang1/2 concentrations remained unchanged. No mutations were detected in the genes analyzed. CONCLUSIONS: Our data suggest that sartans are a safe therapeutic alternative in ACEI-AAE patients. Increased concentrations of VEGF-A, VEGF-C, and sPLA2 in ACEI-AAE patients suggest a possible role of these mediators in the pathogenesis of ACEI-AAE.

Angiotensin-converting enzyme inhibitor-associated angioedema: from bed to bench

BACKGROUND: Angiotensin-converting enzyme inhibitor-associated angioedema (ACEI-AAE) affects 0.1%-0.7% of patients treated with ACEIs. While previous research suggests that angioedema attacks result from increased vascular permeability, the pathogenesis is not completely understood. OBJECTIVE: This study aimed to describe the clinical, genetic, and laboratory parameters of ACEI-AAE patients and to investigate the role of vascular endothelial growth factors A and C (VEGF-A and VEGF-C), angiopoietins 1 and 2 (Ang1/Ang2), and secretory phospholipase A2 (sPLA2) in the pathogenesis of ACEI-AAE. METHODS: The clinical and laboratory data of ACEI-AAE patients were collected from 2 angioedema reference centers. Healthy volunteers and ACEI-treated patients without angioedema were enrolled to compare laboratory parameters. Genetic analyses to detect mutations in the genes SERPING1, ANGPT1, PLG, and F12 were performed in a subset of patients. RESULTS: A total of 51 patients (57% male) were diagnosed with ACEI-AAE. The average time to onset of symptoms from the start of ACEI therapy was 3 years (range, 30 days-20 years). The most commonly affected sites were the lips (74.5%), tongue (51.9%), and face (41.2%). Switching from ACEIs to sartans was not associated with an increased risk of angioedema in patients with a history of ACEIAAE. VEGF-A, VEGF-C, and sPLA2 plasma levels were higher in ACEI-AAE patients than in the controls. Ang1/2 concentrations remained unchanged. No mutations were detected in the genes analyzed. CONCLUSIONS: Our data suggest that sartans are a safe therapeutic alternative in ACEI-AAE patients. Increased concentrations of VEGF-A, VEGF-C, and sPLA2 in ACEI-AAE patients suggest a possible role of these mediators in the pathogenesis of ACEI-AAE

ANTECEDENTES: El angioedema asociado al consumo de inhibidores de la enzima convertidora de angiotensina (IECA-AAE) ocurre en el 0,1%-0,7% de los pacientes tratados con IECA. Aunque se sugiere que los ataques de angioedema son el resultado de una mayor permeabilidad vascular, la patogénesis de este proceso no está plenamente esclarecida. OBJETIVO: En este trabajo se estudiaron los parámetros clínicos, genéticos y de laboratorio de pacientes con IECA-AAE, así como el papel de los factores de crecimiento endotelial vascular A y C (VEGF-A y VEGF-C), las angiopoyetinas 1 y 2 (Ang1/Ang2) y la fosfolipasa secretora A2 (sPLA2). MÉTODOS: Se recogieron datos clínicos y de laboratorio de pacientes con IECA-AAE procedentes de dos centros de referencia en angioedema. Se utilizaron pacientes control, que incluyeron a voluntarios sanos y a pacientes tratados con IECA sin angioedema, para comparar las concentraciones de los parámetros de laboratorio. Finalmente, se realizó un análisis genético en un subconjunto de pacientes para detectar mutaciones en los genes SERPING1, ANGPT1, PLG y F12. RESULTADOS: Se diagnosticaron a 51 pacientes (57% hombres) con IECA-AAE. El tiempo promedio para el inicio de los síntomas desde el comienzo del tratamiento con IECA fue de 3 años (rango de 30 días a 20 años). Los lugares más comúnmente afectados fueron: labios (74,5%), lengua (51,9%) y cara (41,2%). El cambio de IECA a ARA-II no se asoció con un mayor riesgo de angioedema en pacientes con antecedentes de IECA-AAE. Los niveles plasmáticos de VEGF-A, VEGF-C y sPLA2 fueron más altos en pacientes con IECA-AAE que en los controles. No se detectaron cambios en las concentraciones de Ang1/Ang2, ni se detectaron mutaciones en los genes analizados. CONCLUSIONES: Nuestros datos sugieren que los ARA-II pueden ser una alternativa terapéutica segura en pacientes con IECA-AAE. El aumento de las concentraciones de VEGF-A, VEGF-C y sPLA2 en pacientes con ACEI-AAE sugiere un posible papel de estos mediadores en la patogénesis de esta enfermedad

Elevated plasma levels of vascular permeability factors in C1 inhibitor-deficient hereditary angioedema.

BACKGROUND: Hereditary angioedema with C1 inhibitor deficiency (C1-INH-HAE) is a rare inherited genetic disease characterized by recurrent swelling episodes of the skin, gastrointestinal tract, and upper airways. Angioedema attacks result from increased vascular permeability due to the release of bradykinin from high molecular weight kininogen. Currently, there are no biomarkers predicting the frequency of angioedema attacks. Vascular permeability is modulated by several factors, including vascular endothelial growth factors (VEGFs) and angiopoietins (Angs). As increased circulating levels of VEGFs and Angs have been observed in diseases associated with higher vascular permeability (e.g., systemic capillary leak syndrome and sepsis), we sought to analyze plasma concentrations of VEGFs and Angs in patients with C1-INH-HAE. METHODS: Sixty-eight healthy controls and 128 patients with C1-INH-HAE were studied. Concentrations of angiogenic (VEGF-A, Ang1, Ang2), anti-angiogenic (VEGF-A165b ) and lymphangiogenic (VEGF-C) factors were evaluated by ELISA. C1-INH functional activity was assessed by EIA. RESULTS: Plasma concentrations of VEGF-A, VEGF-C, Ang1, and Ang2 were higher in patients with C1-INH-HAE in remission than in healthy controls. Concentration of VEGF-A was further increased in patients with lower C1-INH functional activity. Patients with C1-INH-HAE experiencing more than 12 angioedema attacks per year were characterized by higher plasma levels of VEGF-A, VEGF-C, and Ang2 compared with the other patients. CONCLUSIONS: We hypothesize that VEGFs and Angs induce a state of 'vascular preconditioning' that may predispose to angioedema attacks. In addition, the identification of increased plasma levels of VEGFs and Angs in patients with C1-INH-HAE may prompt the investigation of VEGFs and Angs as biomarkers of C1-INH-HAE severity.

A unique case of angioedema with anti-C1 inhibitor antibodies and normal C1 inhibitor levels

No disponible

Placental cortisol and cord serum IGFBP-2 concentrations are important determinants of postnatal weight gain.

There is a need to identify simple biochemical markers at birth that may predict subjects at risk of growth failure and metabolic complications in later life. Limited research to date has been performed on relationships of specific biochemical determinants at birth with postnatal weight gain and growth. We proposed to establish whether placental cortisol and IL-6 concentrations and cord serum IGF-II and IGFBP-2 concentrations influenced postnatal growth. We followed up from pregnancy 23 IUGR and 37 AGA subjects, and determined placental cortisol and IL-6 concentrations, and cord serum IGF-II, and IGFBP-2 concentrations at birth. We obtained height and weight measurements at 3, 6, 12, 24 months and 5 years of age in 20 IUGR and 15 AGA subjects of comparable gestational age. A multiple linear regression model was designed to establish the effect of the placental and cord serum peptides on postnatal linear growth and weight gain. All IUGR subjects had catch-up growth before 2 years of age. Placental cortisol concentration correlated positively with weight gain during the first 5 years of postnatal growth (P<0.05). Subjects with the highest placental cortisol concentrations were those who showed a greater increase in weight. Cord serum IGFBP-2 concentrations correlated positively with weight gain throughout the 5 year observation period (P:0.003). The subjects with the highest concentrations showed a greater weight gain. Placental cortisol and cord serum IGFBP-2 concentrations were related to postnatal weight gain, suggesting that the fetal environment has long-term effects on growth.

Icatibant treatment for acquired C1-inhibitor deficiency: a real-world observational study.

Icatibant, a bradykinin B2 receptor antagonist, is an established treatment for acute attacks of hereditary angioedema (HAE) with C1-inhibitor (C1-INH) deficiency. We describe our experience with icatibant in eight patients with angioedema because of acquired C1-INH deficiency (AAE). Forty-eight moderate-to-severe attacks were treated with subcutaneous icatibant 30 mg; two moderate attacks resolved without treatment. The median (range) duration of treated attacks (onset to complete resolution) was 9.33 (1.67-39.00) h; durations of the untreated attacks were 72 and 96 h. Symptom improvement following icatibant treatment occurred in 0.5 (0.25-2.10) h and complete resolution in 6.75 (0.50-30.75) h. A single icatibant injection achieved complete symptom resolution in 47 attacks; one facial attack required a second injection. One peripheral attack responded less quickly than other treated attacks. Five patients reported transient injection site reactions. Icatibant appeared to provide effective symptom relief and was generally well tolerated.

Are mast cells MASTers in HIV-1 infection?

HIV-1 gp120 interacts with IgE V(H)3(+) on the surface of human basophils and mast cells (Fc epsilon RI(+) cells), acting as a viral immunoglobulin superantigen. gp120 from different clades induces mediator release from Fc epsilon RI(+) cells. gp120 also induces IL-4 and IL-13 synthesis in human basophils. The chemokine receptors CCR3 and CXCR4, which are coreceptors of HIV-1 infection, are expressed by human Fc epsilon RI(+) cells. HIV-1 Tat protein is a potent chemoattractant for basophils and lung mast cells, interacting with CCR3. Incubation of basophils with Tat protein upregulates the surface expression of the CCR3 receptor. There is evidence that human Fc epsilon RI(+) cells could be infected in vitro by M-tropic HIV-1 strains.

Histamine-induced activation of human lung macrophages.

BACKGROUND: Histamine plays a central role in the pathogenesis of allergic and inflammatory diseases by modulating vascular and airway responses. Increasing evidence suggests that histamine also regulates the function of inflammatory and immune cells. Macrophages are primarily involved in inflammatory diseases of the lung. We explored the ability of low concentrations of histamine to induce the release of proinflammatory mediators from human lung macrophages. METHODS: Macrophages purified (> 95%) from lung parenchyma by Percoll density gradients and adherence to polystyrene dishes were incubated (37 degrees C, 2-24 h) with histamine (10(-9)-10(-6) M). At the end of incubation, the release of beta-glucuronidase and IL-6 was determined. RESULTS: Histamine induced a concentration-dependent release of beta-glucuronidase and IL-6 with a maximum release after 2 and 6 h of incubation, respectively. Exocytosis induced by histamine was noncytotoxic and was Ca(2+)- and temperature-dependent. The effect of histamine was inhibited by the H(1) receptor antagonist fexofenadine but not by the H(2) antagonist ranitidine. CONCLUSIONS: These data indicate that histamine is an effective stimulus for exocytosis and cytokine production from human lung macrophages. These effects are inhibited by pharmacological concentrations of fexofenadine. Our results suggest that histamine may contribute to the long-term evolution of lung inflammation and tissue remodelling in allergic diseases by modulating the production of proinflammatory and immunoregulatory mediators by macrophages.

Role of human FcepsilonRI+ cells in HIV-1 infection.

Enhanced serum IgE levels in adults and children with HIV-1 infection could be a marker of poor prognosis. HIV-1 infection is believed to involve a switch toward a "TH2-like" cytokine pattern. HIV-1 gp120 from different clades is a potent stimulus for histamine release from human basophils and mast cells. Gp120 also induces IL-4 and IL-13 synthesis from basophils. It functions as a viral superantigen by interacting with the VH3 region of IgE to induce mediator release from human FcepsilonRI+ cells. The chemokine receptor CCR3, which binds the chemokines eotaxin and RANTES, is expressed by basophils and lung mast cells. By interacting with the CCR3 receptor on FcepsilonRI+ cells, HIV-1 Tat protein is a potent chemoattractant for basophils and lung mast cells. Tat protein also induces IL-4 and IL-13 release from basophils. Incubation of basophils with Tat protein upregulates the surface expression of the CCR3 receptor, a co-receptor of HIV-1 infection. Extracellular Tat affects the directional migration of human FcepsilonRI+ cells, CCR3 expression and TH2 cytokines release. We have shown that HIV-1 proteins gp120 and Tat trigger the release of cytokines critical for TH2 polarization from FcepsilonRI+ cells through two distinct mechanisms. In addition, Tat upregulates the beta-chemokine receptor CCR3, making FcepsilonRI+ cells more susceptible to infection with CCR3 tropic HIV-1 isolates.

Human mast cells and basophils in HIV-1 infection.

Mast cells and basophils (FcvarepsilonRI(+) cells) are classically involved in allergic disorders. HIV-1 glycoprotein gp120 acts as a viral superantigen by interacting with the heavy chain, variable 3 (V(H)3) region of IgE to induce cytokine release from FcvarepsilonRI(+) cells. The chemokine receptors CCR3 and CXCR4, co-receptors for HIV-1, are expressed by FcvarepsilonRI(+) cells. Via its interaction with CCR3, HIV-1 transactivation (Tat) protein is a potent chemoattractant for FcvarepsilonRI(+) cells. Incubation of basophils with Tat protein upregulates the surface expression of the CCR3 receptor. There is some evidence that human FcvarepsilonRI(+) cells could be infected in vitro by M-tropic HIV-1 strains.